Rational combinations of radiation and chemotherapy which enhance tumor response and minimize normal tissue damage have not been derived clinically because of the lack of experimental data. This project will apply quantitative endpoints in normal tissues and in several tumors in the mouse to the measurement of the dose modification or dose effect factors which occur when radiation interacts with chemotherapy, administered either before or after the irradiation at various time intervals. These studies, conducted in 8 normal tissues and 4 mouse tumor systems, will determine which of 8 common and typical cancer chemotherapeutic agents enhance radiation response in normal tissue and/or in tumor. The dose effect factors will be compared and the effect on therapeutic ratio determined. Time intervals between drug delivery and irradiation will be varied in order to determine the optimum interval for maximum tumor enhancement and minimum normal tissue damage. When enhanced response is noted, its nature and basic mechanism of action will be explored. In order to relate the mouse tumor endpoints to potential for effects in human tumors, quantitative experiments will also be carried out in a group of selected human tumors, transplanted to immunodeficient mice.